Chronic relapsing experimental allergic encephalomyelitis (CREAE) in the mouse is a good animal model for the human disease multiple sclerosis (MS). We propose to use this model to investigate two major questions in the human disease: 1. What role does recognition of autologous major histocompatibility complex (MHC) antigens play in the development of the disease? and 2. What factors may result in an exacerbation of disease symptoms? Utilizing both an adoptive transfer model of CREAE and an in vitro glial cell culture system we will address the above questions with the following experiments. We propose to: 1. Investigate the ability of T cells reactive to syngeneic Class II MHC antigens to destroy Class II expressing glial cells. 2. Investigate the in vivo effects of Class II reactive T cells on the course of CREAE. 3. Investigate the effects of Interferon-gamma (INF-gamma) on CREAE. 4. Investigate the effects of antibody to INF-gamma on this autoimmune disease. We hope the results from the above experiments will allow us to better understand the pathogenesis of CREAE and perhaps also some mechanisms that may be important in MS.